Medical Pathology Commons^™

Uveitis-Mediated Immune Cell Invasion Through The Extracellular Matrix Of The Lens Capsule, Jodirae Dedreu, Sonali Pal-Ghosh, Mary J Mattapallil, Rachel R Caspi, Mary Ann Stepp, A Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While the eye is considered an immune privileged site, its privilege is abrogated when immune cells are recruited from the surrounding vasculature in response to trauma, infection, aging, and autoimmune diseases like uveitis. Here, we investigate whether in uveitis immune cells become associated with the lens capsule and compromise its privilege in studies of C57BL/6J mice with experimental autoimmune uveitis. These studies show that at D14, the peak of uveitis in these mice, T cells, macrophages, and Ly6G/Ly6C+ immune cells associate with the lens basement membrane capsule, burrow into the capsule matrix, and remain integrated with the capsule as immune …

Extracellular Matrix Guidance Of Autophagy: A Mechanism Regulating Cancer Growth, Carolyn Chen, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The extracellular matrix (ECM) exists as a dynamic network of biophysical and biochemical factors that maintain tissue homeostasis. Given its sensitivity to changes in the intra- and extracellular space, the plasticity of the ECM can be pathological in driving disease through aberrant matrix remodelling. In particular, cancer uses the matrix for its proliferation, angiogenesis, cellular reprogramming and metastatic spread. An emerging field of matrix biology focuses on proteoglycans that regulate autophagy, an intracellular process that plays both critical and contextual roles in cancer. Here, we review the most prominent autophagic modulators from the matrix and the current understanding of the …

Interferon Gamma Release Assay Mitogen Responses In Covid-19, Dagan Coppock, Claire E. Zurlo, Jenna M. Meloni, Sara L. Goss, John J. Zurlo, Matthew A. Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Elevated cytokine release and T cell exhaustion have been associated with COVID-19 disease severity. T cell activity may be indirectly measured through interferon gamma release assays (IGRAs), which use mitogen stimulation of T lymphocytes as a positive control. In our institution, an unexpectedly high rate of indeterminate IGRAs was noted in COVID-19–positive patients. We aimed to evaluate the clinical characteristics associated with indeterminate IGRA results and the difference in mitogen responses between COVID-19–positive and COVID-19–negative patients.

Methods

We reviewed all patients, regardless of COVID status, who were admitted between March 1, 2020, and May 31, 2020, and for whom …

Incidence Of Tuberculosis In The Association Of South-East Asia Nation (Asean) Countries And Its Relation With Health Expenditure: A Secondary Data Analysis., Vaanita Shanmuham, Jeevan K. Shetty, Venkatesh Ramaswamy Naik

Manipal Journal of Nursing and Health Sciences

Introduction: Tuberculosis (TB) is an infectious disease that mainly affects the lungs. ASEAN is responsible for the high incidence of tuberculosis recorded worldwide. Therefore, this study analyses the trend of tuberculosis and its association with per capita health expenditure in ASEAN.

Methods: The incidence of tuberculosis and the per capita health expenditure are collected from Global Health Observatory resources and World Bank Organization. The data were interpreted using SPSS Software Version 23 and the results were presented in graphs and tables.

Results: Six ASEAN countries showed a declining trend, three countries had a fluctuating trend, and one country had an …

Evaluation Of Contemporary Echocardiographic And Histomorphology Parameters In Predicting Mortality In Patients With Endomyocardial Biopsy-Proven Cardiac Al Amyloidosis, Efstratios Koutroumpakis, Adam Niku, Christopher K Black, Abdelrahman Ali, Humaira Sadaf, Juhee Song, Nicolas Palaskas, Cezar Iliescu, Jean-Bernard Durand, Syed Wamique Yusuf, Hans C Lee, L Maximilian Buja, Anita Deswal, Jose Banchs

Faculty, Staff and Student Publications

INTRODUCTION: This study examined the role of echocardiographic and cardiac histomorphology parameters in predicting mortality in patients with cardiac AL amyloidosis.

METHODS: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images and endomyocardial biopsy samples were processed for myocardial strain analysis and a detailed histomorphology characterization.

RESULTS: Of 43 patients; 44% were women and 63% white. Median age was 65 years; 51% underwent stem cell transplantation (SCT). Thirty patients (70%) died during follow up (median follow up: 4.1 years). Lower LA strain (

CONCLUSION: Lower LA strain …

Career Transitions: Reflections Of Former Chairs And Academic Health Center Leaders, David N Bailey, L Maximilian Buja, Avrum I Gotlieb, Deborah E Powell, Fred Sanfilippo

Faculty, Staff and Student Publications

The 2022 Association of Pathology Chairs Annual Meeting included a live discussion session and a pre-meeting recorded panel webinar sponsored by the Senior Fellows Group (former chairs of academic departments of pathology who have remained active in the Association of Pathology Chairs). The presentation was focused on transition planning for academic health center leaders. Each of the discussion group panelists had served as a pathology department chair as well as in more senior leadership positions, and they provided perspectives based upon their personal experiences. It was noted that such positions are often "at will" appointments of indeterminate length and that …

Clinicopathological Correlations In Heart Transplantation Recipients Complicated By Death Or Re-Transplantation, Michelle M Mcdonald, Maks Mihalj, Bihong Zhao, Sriram Nathan, Stanislava Matejin, Giulia Ottaviani, Mateja K Jezovnik, Rajko Radovancevic, Biswajit Kar, Igor D Gregoric, L Maximilian Buja

Faculty, Staff and Student Publications

PURPOSE: This study aimed to identify and correlate pathological findings with clinical outcomes in patients after orthotopic heart transplantation (OHT) who either died or underwent a re-transplantation.

METHODOLOGY AND STUDY DESIGN: Single-center retrospective analysis of primary OHT patients who died or were re-transplanted between October 2012 and July 2021. Clinical data were matched with corresponding pathological findings from endomyocardial biopsies on antibody-mediated rejection, cellular rejection, and cardiac allograft vasculopathy. Re-assessment of available tissue samples was performed to investigate acute myocardial injury (AMI) as a distinct phenomenon. These were correlated with clinical outcomes, which included severe primary graft dysfunction. Patients were …

Urinary T Cells Are Detected In Patients With Immune Checkpoint Inhibitor-Associated Immune Nephritis That Are Clonotypically Identical To Kidney T Cell Infiltrates, Shailbala Singh, Leticia C Clemente, Edwin R Parra, Amanda Tchakarov, Chao Yang, Yisheng Li, James P Long, Cassian Yee, Jamie S Lin

Faculty, Staff and Student Publications

Acute kidney injury (AKI) occurs in ~20% of patients receiving immune checkpoint inhibitor (ICI) therapy; however, only 2-5% will develop ICI-mediated immune nephritis. Conventional tests are nonspecific in diagnosing disease pathology and invasive procedures (i.e. kidney biopsy) may not be feasible. In other autoimmune renal diseases, urinary immune cells correlated with the pathology or were predictive of disease activity. Corresponding evidence and analysis are absent for ICI-mediated immune nephritis. We report the first investigation analyzing immune cell profiles of matched kidney biopsies and urine of patients with ICI-AKI. We demonstrated the presence of urinary T cells in patients with immune …

Platelet Micrornas Inhibit Primary Tumor Growth Via Broad Modulation Of Tumor Cell Mrna Expression In Ectopic Pancreatic Cancer In Mice, Jeremy G.T. Wurtzel, Sophia Lazar, Sonali Sikder, Kathy Q Cai, Igor Astsaturov, Andrew S Weyrich, Jesse W Rowley, Lawrence E. Goldfinger

Department of Medicine Faculty Papers

We investigated the contributions of platelet microRNAs (miRNAs) to the rate of growth and regulation of gene expression in primary ectopic tumors using mouse models. We previously identified an inhibitory role for platelets in solid tumor growth, mediated by tumor infiltration of platelet microvesicles (microparticles) which are enriched in platelet-derived miRNAs. To investigate the specific roles of platelet miRNAs in tumor growth models, we implanted pancreatic ductal adenocarcinoma cells as a bolus into mice with megakaryocyte-/platelet-specific depletion of mature miRNAs. We observed an ~50% increase in the rate of growth of ectopic primary tumors in these mice compared to controls …

Dysregulation Of Dna Methylation And Epigenetic Clocks In Prostate Cancer Among Puerto Rican Men, Anders Berglund, Jaime Matta, Jarline Encarnación-Medina, Carmen Ortiz-Sanchéz, Julie Dutil, Raymond Linares, Joshua Marcial, Caren Abreu-Takemura, Natasha Moreno, Ryan Putney, Ratna Chakrabarti, Hui Yi Lin, Kosj Yamoah, Carlos Diaz Osterman, Liang Wang, Jasreman Dhillon, Youngchul Kim, Seung Joon Kim, Gilberto Ruiz-Deya, Jong Y. Park

School of Public Health Faculty Publications

In 2021, approximately 248,530 new prostate cancer (PCa) cases are estimated in the United States. Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. The objective of this study was to assess DNA methylation patterns between aggressive and indolent PCa along with ancestry proportions in 49 H/L men from Puerto Rico (PR). Prostate tumors were classified as aggressive (n = 17) and indolent (n = 32) based on the Gleason score. Genomic DNA samples were extracted by macro-dissection. DNA methylation patterns were assessed using the Illumina EPIC DNA methylation platform. We used ADMIXTURE to estimate global ancestry proportions. …

Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge

Electronic Theses and Dissertations

It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …

Structural Barriers Associated With The Intersection Of Traumatic Stress And Gun Violence: A Case Example Of New Orleans, Rahn Kennedy Bailey, Chikira H. Barker, Amit Grover

School of Medicine Faculty Publications

Gun violence drastically increased in urban cities following the ease of shutdown restric-tions associated with the Coronavirus Pandemic. The association of gun violence and COVID-19 has highlighted the importance of taking a public health perspective, particularly as it relates to impacts on the Black community. In this article we discuss macro-level factors and community traumas in the city of New Orleans, an area that has had longstanding issues related to gun violence. Community structural issues, traumatic stress from disasters, and recommendations to address disparities in social determinants of health are discussed.

Dysregulation Of Mir-21-Associated Mirna Regulatory Networks By Chronic Ethanol Consumption Impairs Liver Regeneration., Austin Parrish, Ankita Srivastava, Egle Juskeviciute, Jan B Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Impaired liver regeneration has been considered as a hallmark of progression of alcohol-associated liver disease. Our previous studies demonstrated that in vivo inhibition of the microRNA (miRNA) miR21 can restore regenerative capacity of the liver in chronic ethanol-fed animals. The present study focuses on the role of microRNA regulatory networks that are likely to mediate the miR-21 action. Rats were chronically fed an ethanol-enriched diet along with pair-fed control animals and treated with AM21 (anti-miR-21), a locked nucleic acid antisense to miR-21. Partial hepatectomy (PHx) was performed and miRNA expression profiling over the course of liver regeneration was assessed. Our …

Stem Signatures Associating Sox2 Antibody Helps To Define Diagnosis And Prognosis Prediction With Esophageal Cancer, Zi-Yang Peng, Qing-Shi Wang, Kai Li, Si-Si Chen, Xiang Li, Guo-Dong Xiao, Shou-Ching Tang, Hong Ren, Zhe Wang, Xin Sun

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: esophageal cancer is one of the deadliest diseases worldwide. Due to the ineffectual screening methods referring to early diagnosis, most people have lost their chance of radical resection when diagnosed with esophageal cancer. This aim of this study was designed to evaluate the latent values of the stem signatures-associated autoantibodies (AABS) in predicting the early diagnosis, and particularly seeking the precise predictive outcomes with sensitive SOX2. We also studied the potential immunotherapeutic targets and prospective long-term prognosis predicators of esophageal cancer.

Methods: The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of …

Limitations Of Available Blood Products For Massive Transfusion During Mass Casualty Events At Us Level 1 Trauma Centers, James Williams, Michael Gustafson, Yu Bai, Samuel Prater, Charles E Wade, Oscar D Guillamondegui, Mansoor Khan, Megan Brenner, Paula Ferrada, Derek Roberts, Tal Horer, David Kauvar, Andrew Kirkpatrick, Carlos Ordonez, Bruno Perreira, Artai Priouzram, Juan Duchesne, Bryan A Cotton

Faculty, Staff and Student Publications

INTRODUCTION: Exsanguination remains a leading cause of preventable death in traumatically injured patients. To better treat hemorrhagic shock, hospitals have adopted massive transfusion protocols (MTPs) which accelerate the delivery of blood products to patients. There has been an increase in mass casualty events (MCE) worldwide over the past two decades. These events can overwhelm a responding hospital's supply of blood products. Using a computerized model, this study investigated the ability of US trauma centers (TCs) to meet the blood product requirements of MCEs.

METHODS: Cross-sectional survey data of on-hand blood products were collected from 16 US level-1 TCs. A discrete …

A Spatial Model Of Hepatic Calcium Signaling And Glucose Metabolism Under Autonomic Control Reveals Functional Consequences Of Varying Liver Innervation Patterns Across Species, Aalap Verma, Alexandra Manchel, Rahul Narayanan, Jan B. Hoek, Babatunde A Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Rapid breakdown of hepatic glycogen stores into glucose plays an important role during intense physical exercise to maintain systemic euglycemia. Hepatic glycogenolysis is governed by several different liver-intrinsic and systemic factors such as hepatic zonation, circulating catecholamines, hepatocellular calcium signaling, hepatic neuroanatomy, and the central nervous system (CNS). Of the factors regulating hepatic glycogenolysis, the extent of lobular innervation varies significantly between humans and rodents. While rodents display very few autonomic nerve terminals in the liver, nearly every hepatic layer in the human liver receives neural input. In the present study, we developed a multi-scale, multi-organ model of hepatic metabolism …

Low-Grade Primary Splenic Cd10-Positive Small B-Cell Lymphoma/Follicular Lymphoma, Rami Abdulbaki, Parastou Tizro, Victor E. Nava, Maria Gomes Da Silva, Joao L. Ascensao

Pathology Faculty Publications

No abstract provided.

Mirna-30e Downregulation Increases Cancer Cell Proliferation, Invasion And Tumor Growth Through Targeting Rps6kb1, Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Zhong-Kun Xia, Yun-Xia Xie, Wen-Jing Liu, Jian-Ge Qiu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Human esophagus carcinoma (EC) is one of the most common malignant tumors, especially in Africa and Asia including China. In EC initiation and progression, genetic and epigenetic aberrations have been reported to play a major role, but the underlying molecular mechanisms are largely unknown. In this study, the miR-30e levels were analyzed in human EC tissues and TCGA databases, and the results demonstrated that miR-30e expression in EC tissues was significantly decreased compared to adjacent normal tissues. To further investigate the role of miR-30e in cancer cells, we found that forced expression of miR-30e dramatically inhibited cell proliferation, invasion, tube …

Simultaneous Brain And Intramedullary Spinal Abscesses In A Patient With Streptococcus Intermedius Infection, David P. Friedman, Joseph Desimone Jr, Aaron Christensen, Matthew Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A male patient in his thirties presented to the hospital with meningismus and altered mental status. Cerebrospinal fluid (CSF) analysis confirmed meningitis, but no microorganisms were identified. Head imaging (MRI) revealed multiple brain abscesses. Surgically-collected brain specimens revealed Gram-positive cocci and subsequently grew Streptococcus intermedius. MRI of the thoracic spine subsequently also identified an intramedullary spinal abscess. While brain abscesses and spinal abscesses caused by S. intermedius have been previously reported, the extent of disseminated disease in the patient was noteworthy.

A Phase Ib Dose Escalation Trial Of Ro4929097 (A Γ-Secretase Inhibitor) In Combination With Exemestane In Patients With Er + Metastatic Breast Cancer (Mbc), Julie A. Means-Powell, Ingrid A. Mayer, Roohi Ismail-Khan, Luis Del Valle, Debra Tonetti, Vandana G. Abramson, Melinda S. Sanders, Richard M. Lush, Claudia Sorrentino, Samarpan Majumder, Lucio Miele

School of Medicine Faculty Publications

Preclinical studies: have demonstrated a complex cross-talk between Notch and estrogen signaling in ERα-positive breast cancer. Gamma-secretase inhibitors (GSIs) are investigational agents that block the cleavage and activation of Notch receptors. In animal models of endocrine-resistant breast cancer, combinations of tamoxifen and GSIs produce additive or synergistic efficacy, while decreasing the intestinal toxicity of GSIs. However, results of a clinical trial of a GSI-endocrine therapy combination in the metastatic setting have not been published to date, nor had the safety of such combinations been investigated with longer term treatment. We conducted a phase 1b dose escalation trial (NCT01149356) of GSI …